Genotoxic and mutagenic activation of aflatoxin B1 by constitutive forms of cytochrome P-450 in rat liver microsomes.
Genotoxic and mutagenic activation of aflatoxin B1 by constitutive forms of cytochrome P-450 in rat liver microsomes.
复制标题
大鼠肝微粒体中细胞色素 P-450 的组成型对黄曲霉毒素 B1 的基因毒性和诱变激活。
DOI：
10.1016/0041-008x(87)90189-x
复制
发表时间：
1987
影响因子：
3.8
通讯作者：
Y. Funae
中科院分区：
文献类型：
--
作者：
Tsutomu Shimada;Sei;S. Imaoka;Y. Funae
在大鼠肝微粒体或重组单加氧酶系统中，研究了细胞色素P-450介导的黄曲霉毒素B1（AFB 1）活化为遗传毒性和致突变产物，随后诱导鼠伤寒沙门氏菌TA 1535/pSK 1002中umu基因的表达。雄性SD大鼠肝微粒体对黄曲霉毒素B1的催化活性是雌性大鼠的1.5倍。此外，激活没有增加，从大鼠肝微粒体预处理苯巴比妥，3-甲基胆蒽，多氯联苯混合物，或地塞米松，表明细胞色素P-450的组成形式有重要作用的激活黄曲霉毒素B1在大鼠肝微粒体。用从未处理的大鼠和苯巴比妥和3-甲基胆蒽处理的大鼠肝微粒体中纯化的15种细胞色素P-450，发现未处理的雄性大鼠的3种同工酶和未处理的雌性大鼠的1种同工酶在代谢黄曲霉毒素B_（11）为遗传毒性产物中具有高反应性。从诱导剂处理的大鼠中分离的细胞色素P-450形式的活性相对较低。umu基因的诱导表达与艾姆斯/S.在TA 98系统中，AFB 1的代谢产物在单加氧酶系统中被激活，提示细胞色素P-450的组成型在AFB 1的遗传毒性和致突变激活中起主要作用。
Cytochrome P-450-mediated activation of aflatoxin B1(AFB1) to genotoxic and mutagenic products which subsequently cause induction of an umu gene expression in Salmonella typhimurium TA1535/pSK1002 has been studied in a rat liver microsomal or reconstituted monooxygenase system. Liver microsomes from male Sprague-Dawley rats had a 1.5-fold higher activity to catalyze AFB1than did those from female rats. In addition, the activation was not increased in liver microsomes from rats pretreated with phenobarbital, 3-methylcholanthrene, a polychlorinated biphenyl mixture, or dexamethasone, suggesting that the constitutive forms of cytochrome P-450 have important roles for the activation of AFB1in rat liver microsomes. Using 15 forms of cytochrome P-450 purified from liver microsomes of untreated and phenobarbital- and 3-methylcholanthrene-treated rats, three isozymes from untreated male rats and one isozyme from untreated female rats were found to have high reactivities in metabolizing AFB1to genotoxic products. Cytochrome P-450 forms isolated from inducer-treated rats were relatively less active. The close correlation between induction of umu gene expression and mutagenicity with Ames/S. typhimurium TA98 system by activated metabolites of AFB1in the reconstituted monooxygenase system suggested that the constitutive forms of cytochrome P-450 had major roles for genotoxic and mutagenic activation of AFB1in rat liver microsomes.
登录
查看更多内容
DOI：
--
发表时间：
1986-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
T. Shimada;K. Misono;F. Guengerich
通讯作者：
T. Shimada;K. Misono;F. Guengerich
影响因子：
2.9
作者：
GUENGERICH, FP;DANNAN, GA;KAMINSKY, LS
通讯作者：
KAMINSKY, LS
来自成年雄性大鼠肝微粒体的三种高度纯化的细胞色素 P-450 的表征。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ryan,DE;Iida,S;Wood,AW;Thomas,PE;Lieber,CS;Levin,W
通讯作者：
Levin,W
成熟虹鳟鱼肾微粒体细胞色素 P-450 同工酶组成和活性的性别差异。
影响因子：
5.8
作者：
Williams,DE;Masters,BS;Lech,JJ;Buhler,DR
通讯作者：
Buhler,DR
影响因子：
2.9
作者：
WAXMAN, DJ;DANNAN, GA;GUENGERICH, FP
通讯作者：
GUENGERICH, FP